Two Preputial Gland-Secreted Pheromones Evoke Sexually Dimorphic Neural Pathways in the Mouse Vomeronasal System

Abstract

Hexadecanol (16OH) and hexadecyl acetate (16Ac) are two pheromones secreted in a large quantity by mouse preputial glands and act on male and female mice differentially. Yet the underlying molecular and cellular mechanisms remain to be elucidated. In this study, we examined the activation of vomeronasal sensory neurons (VSNs) by these two pheromones and mapped the downstream neural circuits that process and relay their chemosignals. Using the calcium imaging method and immunohistochemistry, we found that a small number of VSNs were activated by 16OH, 16AC, or both in the male and female mice, most of which were located apically in the vomeronasal epithelium, and their numbers did not increase when the concentrations of 16OH and 16Ac were raised by 10,000-fold except that of female VSNs in response to 16OH. In the accessory olfactory bulb (AOB), the two pheromones evoked more c-Fos+ neurons in the anterior AOB (aAOB) than in the posterior AOB (pAOB); and the increases in the number of c-Fos+ neurons in both aAOB and pAOB were dose-dependent; and between sexes, the female AOB responded more strongly to 16OH than to 16Ac whereas the male AOB had the opposite response pattern. This sexual dimorphism was largely retained in the downstream brain regions, including the bed nucleus of the stria terminalis (BNST), the medial amygdaloid nucleus (MeA), the posteromedial cortical amygdaloid nucleus (PMCo), the medial preoptic area (MPA), and the ventromedial hypothalamic nucleus (VmH). Taken together, out data indicate that there is one V1r receptor each for 16OH, 16Ac, or both, and that activation of these receptors evokes sexually dimorphic neural circuits, directing different behavioral outputs and possibly modulating other pheromone-induced responses.

BNSTAVGABA-PVNCRF Circuit Regulates Visceral Hypersensitivity Induced by Maternal Separation in Vgat-Cre Mice

“…Albeit female animals could serve to mimic the common clinical symptoms in female IBS-patients, the variations of estrogen and progesterone in response to CRD may affect the pain perception and underlying pain circuitry during the estrus cycle. In addition, BNST is a sexually dimorphic structure rich in distinctive neuronal subpopulations ( Zhang et al, 2018 ; Liu et al, 2019 ). Accordingly, we only recruited neonatal male mice, which were reared to the postnatal 8 th week for experimentation.…”

Male pheromones and their reception by females are co-adapted to affect mating success in two subspecies of brown rats

“…VNOs were then separated from the nasal septum and embedded in low-melting agarose. The coronal slices were cut at a thickness of 200 μm with a vibratome (Leica VT1200S, Germany) ( Brechbuhl et al 2011 ; Liu et al 2019 ), and the slices were incubated with loading solution (ACSF with 10 μM FURA-2 AM and 0.1% Pluronic F-127). The samples were illuminated with an ion imaging system (Nikon Ti-E, Japan), and the changes in the calcium ratio were monitored.…”

“…The samples were illuminated with an ion imaging system (Nikon Ti-E, Japan), and the changes in the calcium ratio were monitored. For each imaging session, one of the 3 pheromones (10 −5 M 2-heptanone, 10 −7 M MUP13, or 10 −7 M olfactory‐binding protein 3 [OBP3]) ( Guo et al 2018 ) was delivered at a flow rate of 1 mL/min, and 50 mM KCl was applied to verify the viability of the cells at the end of the test ( Zufall and Leinders-Zufall 2007 ; Brechbuhl et al 2011 ; Liu et al 2019 ).…”

Processing of intraspecific chemical signals in the rodent brain

“…Besides selectivity to social stimuli, the medial amygdala displays sexually dimorphic responses, which may be already apparent in the AOB (Liu et al 2019;Baum and Kelliher 2009), as a result of peripubertal steroid signaling that drives the arrangement of functional responses in this area (Bergan et al 2014). The medial amygdaloid nucleus, within the corticomedial amygdala, receives fibers from the AOB and sends efferents to the ventral premammillary nucleus, in addition to the ventrolateral subdivision of the ventromedial hypothalamus.…”

“…Moreover, the activation of chemosensory areas is different. The responses to preputial gland pheromones vary between male and female mice in the AOB, bed nucleus of the stria terminalis, medial amygdala, medial preoptic area, and ventromedial hypothalamus (Liu et al 2019). The medial preoptic area is involved in mediating sexual motivation: in proestrus rats, pheromone-driven activity in this area is mediated by GABA and is modulated by the time of the day, being enhanced during nighttime, during which copulation occurs (Grigorjev and Munaro 1999).…”